1. Field of the Invention
The present invention relates generally to inflammatory cytokines, matrix metalloproteinases and maintenance of extracellular matrix and discloses use of intracellular interleukin-1 (IL-1) receptor antagonists in the inhibition of degradation of extracellular matrix. More specifically, the present invention discloses the use of peptides of intracellular isoform of IL-1 receptor antagonist in the inhibition of tissue degradation and treatment of chronic inflammatory disorders.
2. Description of the Related Art
IL-1 is a cytokine which stimulates cells to release pro-inflammatory proteins resulting in joint inflammation and destruction. Because of its central role in causing joint destruction, interleukin-1 is now a target for the treatment of arthritis. IL-1 has a naturally occurring inhibitory protein called IL-1 receptor antagonist (IL-1ra). This inhibitory protein has two isoforms, a secreted isoform (sIL-1ra) and an intracellular isoform (icIL-1ra), which results from alternate splicing of RNA encoding the amino-termini. The role of the secreted isoform of IL-1 receptor antagonist in the inhibition of inflammatory effects of IL-1 is due to its ability to occupy the receptor without transducing a signal.
The ability of sIL-1ra to ameliorate the development of arthritis has been well established. However, almost nothing is known about the function or mode of action of the intracellular isoform of IL-1 receptor antagonist, especially in the regulation of inflammation and degradation of extracellular matrix and the utility of such IL-1 receptor antagonists. The present invention fulfills this long-standing need and desire in the art.